Young women with an acute myocardial infarction (AMI) represent an extreme phenotype in ischemic heart disease risk and, at the same time, constitute a large understudied group with excess mortality risk compared with similarly aged men. This combination of adverse risk and inadequate investigation provides a critically important opportunity to address the care and outcomes of young women with AMI to uncover key biological and environmental determinants of their prognosis. Accordingly, we propose the first large, comprehensive, observational study of young women with AMI (YWAMI). YWAMI will include 2,000 women, 18-55 years of age, with AMI and a comparison cohort of 1,000 men enrolled over 3 years from 88 hospitals across the United States and in Canada. To accomplish these aims we have assembled a team of leading researchers in sex disparities in cardiovascular disease, outcomes research, epidemiology, statistics, genetics, biomarker research, health status measurement, psychosocial research, cardiology, and emergency medicine. Our Specific Aims are to: 1) characterize sex differences in outcomes following AMI (including mortality, hospitalization and health status); 2) determine sex differences in the prevalence of demographic, clinical, and psychosocial risk factors; 3) determine sex differences in quality of care; and 4) determine sex differences in the prevalence of selected biological factors (including sex hormones, biomarkers and genetic variations). We will characterize these differences in great detail and elucidate the biological and environmental factors that are responsible for disparities in outcomes. The analyses from all four aims will be used to develop clinically useful risk-stratification models for young AMI patients, explain sex differences in outcomes and identify targets for intervention. We will also bank serum and DMA from each subject, creating a resource for anticipated future studies of the molecular biology of AMI in young women and men. We will work with the American College of Cardiology, the American Heart Association and VHA, Inc. to disseminate findings from this study that can be used to improve the prevention, care, and outcomes for young women and men with AMI. Public Health Implications: Overall, although heart disease in young women accounts for as many deaths as breast cancer, few studies have addressed the biological, environmental and social factors that influence their outcome. Young women with heart attacks have a higher risk of dying than similarly aged men. We propose to conduct the largest, most comprehensive study of young women with heart attacks to identify the key determinants of their recovery and discover knowledge that will assist us in improving their care.